MP1_DROME
ID MP1_DROME Reviewed; 400 AA.
AC A0A126GUP6; B7Z0T0; E8NHA1; Q9Y157;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 11-MAY-2016, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Melanization protease 1 {ECO:0000303|PubMed:16861233};
DE EC=3.4.21.- {ECO:0000305|PubMed:16861233};
DE Flags: Precursor;
GN Name=MP1 {ECO:0000312|FlyBase:FBgn0027930};
GN ORFNames=CG1102 {ECO:0000312|FlyBase:FBgn0027930};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:AAD38586.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAD38586.1};
RC TISSUE=Head {ECO:0000312|EMBL:AAD38586.1};
RX PubMed=10731138; DOI=10.1126/science.287.5461.2222;
RA Rubin G.M., Hong L., Brokstein P., Evans-Holm M., Frise E., Stapleton M.,
RA Harvey D.A.;
RT "A Drosophila complementary DNA resource.";
RL Science 287:2222-2224(2000).
RN [4] {ECO:0000312|EMBL:ADX35956.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 96-400.
RC STRAIN=Berkeley {ECO:0000312|EMBL:ADX35956.1};
RC TISSUE=Head {ECO:0000312|EMBL:ADX35956.1};
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (FEB-2011) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=16861233; DOI=10.1074/jbc.m601642200;
RA Tang H., Kambris Z., Lemaitre B., Hashimoto C.;
RT "Two proteases defining a melanization cascade in the immune system of
RT Drosophila.";
RL J. Biol. Chem. 281:28097-28104(2006).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=18854145; DOI=10.1016/j.devcel.2008.08.017;
RA Tang H., Kambris Z., Lemaitre B., Hashimoto C.;
RT "A serpin that regulates immune melanization in the respiratory system of
RT Drosophila.";
RL Dev. Cell 15:617-626(2008).
RN [7] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=22227521; DOI=10.1038/emboj.2011.476;
RA Nam H.J., Jang I.H., You H., Lee K.A., Lee W.J.;
RT "Genetic evidence of a redox-dependent systemic wound response via Hayan
RT protease-phenoloxidase system in Drosophila.";
RL EMBO J. 31:1253-1265(2012).
CC -!- FUNCTION: Serine protease which plays an essential role in the
CC melanization immune response by acting downstream of sp7 to activate
CC prophenoloxidase (PPO1) (PubMed:16861233). May function in diverse
CC Hayan-dependent PPO1-activating cascades that are negatively controlled
CC by different serpin proteins; Spn27A in the hemolymph and Spn77BA in
CC the trachea (PubMed:18854145, PubMed:16861233). Regulation of
CC melanization and PPO1 activation appears to be largely independent of
CC the Toll signaling pathway (PubMed:16861233).
CC {ECO:0000269|PubMed:16861233, ECO:0000269|PubMed:18854145}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=E {ECO:0000312|FlyBase:FBgn0027930};
CC IsoId=A0A126GUP6-1; Sequence=Displayed;
CC Name=A {ECO:0000312|FlyBase:FBgn0027930};
CC IsoId=A0A126GUP6-2; Sequence=VSP_058613;
CC Name=C {ECO:0000312|FlyBase:FBgn0027930};
CC IsoId=A0A126GUP6-3; Sequence=VSP_058614;
CC -!- DOMAIN: The clip domain consists of 35-55 residues which are 'knitted'
CC together usually by 3 conserved disulfide bonds forming a clip-like
CC compact structure. {ECO:0000255|PROSITE-ProRule:PRU01236}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown is semi-pupal lethal,
CC with 50% of pupae dying at the late pupal stage or during eclosion
CC (PubMed:16861233). Adults display impaired melanization at the site of
CC septic infection (septic injury) using either Gram-negative (E.coli) or
CC Gram-positive bacteria (M.luteus) (PubMed:16861233). No significant
CC increase in PPO1 activity after septic injury using fungi (B.bassiana)
CC and bacteria (PubMed:16861233). Survival and induction of antimicrobial
CC peptides (Dpt and Drs) is not affected after bacterial or fungal
CC infection (PubMed:16861233). Aseptic wounding has no effect on survival
CC (PubMed:22227521). {ECO:0000269|PubMed:16861233,
CC ECO:0000269|PubMed:22227521}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. CLIP subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01236}.
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DR EMBL; AE014297; AAF52151.3; -; Genomic_DNA.
DR EMBL; AE014297; AAN13300.2; -; Genomic_DNA.
DR EMBL; AE014297; ALI30526.1; -; Genomic_DNA.
DR EMBL; AF145611; AAD38586.1; -; mRNA.
DR EMBL; BT125977; ADX35956.1; -; mRNA.
DR RefSeq; NP_001138002.1; NM_001144530.2. [A0A126GUP6-3]
DR RefSeq; NP_001303421.1; NM_001316492.1. [A0A126GUP6-1]
DR RefSeq; NP_649450.3; NM_141193.4. [A0A126GUP6-2]
DR AlphaFoldDB; A0A126GUP6; -.
DR SMR; A0A126GUP6; -.
DR STRING; 7227.FBpp0290158; -.
DR MEROPS; S01.B31; -.
DR GlyGen; A0A126GUP6; 2 sites.
DR DNASU; 40541; -.
DR EnsemblMetazoa; FBtr0078903; FBpp0078543; FBgn0027930. [A0A126GUP6-2]
DR EnsemblMetazoa; FBtr0300936; FBpp0290158; FBgn0027930. [A0A126GUP6-3]
DR EnsemblMetazoa; FBtr0445313; FBpp0401490; FBgn0027930. [A0A126GUP6-1]
DR GeneID; 40541; -.
DR KEGG; dme:Dmel_CG1102; -.
DR UCSC; CG1102-RA; d. melanogaster.
DR CTD; 40541; -.
DR FlyBase; FBgn0027930; MP1.
DR VEuPathDB; VectorBase:FBgn0027930; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000163739; -.
DR OMA; DFISPVC; -.
DR BioGRID-ORCS; 40541; 0 hits in 1 CRISPR screen.
DR ChiTaRS; MP1; fly.
DR GenomeRNAi; 40541; -.
DR PRO; PR:A0A126GUP6; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0027930; Expressed in arthropod fat body and 13 other tissues.
DR ExpressionAtlas; A0A126GUP6; differential.
DR Genevisible; B7Z0T0; DM.
DR GO; GO:0004175; F:endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017171; F:serine hydrolase activity; HDA:FlyBase.
DR GO; GO:0004252; F:serine-type endopeptidase activity; ISM:FlyBase.
DR GO; GO:0035006; P:melanization defense response; IMP:FlyBase.
DR GO; GO:0006508; P:proteolysis; ISM:FlyBase.
DR GO; GO:0009620; P:response to fungus; HEP:FlyBase.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 3.30.1640.30; -; 1.
DR InterPro; IPR022700; CLIP.
DR InterPro; IPR038565; CLIP_sf.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF12032; CLIP; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00680; CLIP; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS51888; CLIP; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Disulfide bond; Glycoprotein; Hydrolase;
KW Metal-binding; Protease; Reference proteome; Serine protease; Signal;
KW Zymogen.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..137
FT /note="Activation peptide"
FT /evidence="ECO:0000250|UniProtKB:Q9V3Z2"
FT /id="PRO_0000438112"
FT CHAIN 138..400
FT /note="Melanization protease 1"
FT /evidence="ECO:0000305"
FT /id="PRO_5007270038"
FT DOMAIN 28..91
FT /note="Clip"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DOMAIN 138..399
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 98..120
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 98..119
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 183
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 248
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 346
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT BINDING 201
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O97366"
FT BINDING 203
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O97366"
FT BINDING 206
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O97366"
FT BINDING 209
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O97366"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 29..90
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 39..70
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 45..91
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 130..268
FT /evidence="ECO:0000250|UniProtKB:Q9VB68"
FT DISULFID 168..184
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 210..220
FT /evidence="ECO:0000250|UniProtKB:Q9VB68"
FT DISULFID 315..332
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 342..375
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT VAR_SEQ 79..88
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000305"
FT /id="VSP_058613"
FT VAR_SEQ 79..88
FT /note="EKHFCFTNVQ -> VSTPLKSCG (in isoform C)"
FT /evidence="ECO:0000305"
FT /id="VSP_058614"
SQ SEQUENCE 400 AA; 44939 MW; 4ED78A24A45BC3CA CRC64;
MEPHFFFTVL WMLLMGTSST YAQEIFGYCR TPDENSGTCI NLRECGYLFE LLQSEEVTEQ
DRRFLQASQC GYRNGQVLEK HFCFTNVQIC CANSRMRNQQ PQWGNHPQPT QTTKPTKRSG
TKLLPMAPNC GENFGDRVVG GNETTKREFP WMALIEYTKP GNVKGHHCGG SLINHRYVLT
AAHCVSAIPS DWELTGVRLG EWDASTNPDC TVGKNGRRDC NEPYVDYPVE ERIPHPQYPG
NSRDQLNDIA LLRLRDEVQY SDFILPVCLP TLASQHNNIF LGRKVVVAGW GRTETNFTSN
IKLKAELDTV PTSECNQRYA TQRRTVTTKQ MCAGGVEGVD SCRGDSGGPL LLEDYSNGNS
NYYIAGVVSY GPTPCGLKGW PGVYTRVEAY LNWIENNVRA
